Lens-related ocular changes in fetal rats following in-utero exposure to elexacaftor-tezacaftor-ivacaftor

Background and Objective: Elexacaftor-tezacaftor-ivacaftor (ETI) is a drug treatment for cystic fibrosis that is debatable for use in pregnant women. Fetal ocular changes following prenatal exposure and while breastfeeding to ETI have been reported. The aim of this study was to assess eye development in rat fetuses following in-utero exposure to ETI. Design and Methods: Eyes from Sprague Dawley rats born to dams given clinically relevant ETI or sham treatment from embryonic day 12-19 (E12-E19) were investigated using histology and optical coherence tomography (OCT). Results: Lens thickness was higher in the ETI-exposure group, as measured by OCT (p = 0.0003). Lens cavities were observed in both groups, but the median individual lens cavities area was higher in the ETI-exposed eyes (p < 0.0001), as measured by histology. Conclusion: In-utero exposure to ETI during E12-E19 was associated with subtle changes to lens anatomy, however the mechanism and clinical significance of this observation requires further investigation.